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Showing papers by "Blaise Genton published in 2011"


Journal ArticleDOI
TL;DR: Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials and should be integrated hand-in-hand with training on the management of other causes of fever to prevent irrational use of antibiotics.
Abstract: Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (m RDTs) on prescription of anti-malarials in urban Tanzania. The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF) in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of m RDTs in all three hospitals and in six HF. Three HF without m RDTs were selected as matched controls. The use of routine m RDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after m RDT implementation. Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80) in intervention and 32% (9-54) in control HF. For quinine vials, the reduction was 63% (54-72) in intervention and an increase of 2.49 times (1.62-3.35) in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26). The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22%) and control HF (60%) (Risk ratio 0.30, 95%CI 0.14-0.70). Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic prescription increased from 49% before to 72% after intervention (Risk ratio 1.47, 95%CI 1.37-1.59). Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials. Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results. Implementation of m RDT should be integrated hand-in-hand with training on the management of other causes of fever to prevent irrational use of antibiotics.

169 citations


Journal ArticleDOI
TL;DR: The quality of routine microscopy was poor in all health facilities, regardless of their level, and over-diagnosis was massive, with many false positive results reported as very low parasitaemia.
Abstract: Laboratory capacity to confirm malaria cases in Tanzania is low and presumptive treatment of malaria is being practiced widely. In malaria endemic areas WHO now recommends systematic laboratory testing when suspecting malaria. Currently, the use of Rapid Diagnostic Tests (RDTs) is recommended for the diagnosis of malaria in lower level peripheral facilities, but not in health centres and hospitals. In this study, the following parameters were evaluated: (1) the quality of routine microscopy, and (2) the effects of RDT implementation on the positivity rate of malaria test results at three levels of the health system in Dar es Salaam, Tanzania. During a baseline cross-sectional survey, routine blood slides were randomly picked from 12 urban public health facilities in Dar es Salaam, Tanzania. Sensitivity and specificity of routine slides were assessed against expert microscopy. In March 2007, following training of health workers, RDTs were introduced in nine public health facilities (three hospitals, three health centres and three dispensaries) in a near-to-programmatic way, while three control health facilities continued using microscopy. The monthly malaria positivity rates (PR) recorded in health statistics registers were collected before (routine microscopy) and after (routine RDTs) the intervention in all facilities. At baseline, 53% of blood slides were reported as positive by the routine laboratories, whereas only 2% were positive by expert microscopy. Sensitivity of routine microscopy was 71.4% and specificity was 47.3%. Positive and negative predictive values were 2.8% and 98.7%, respectively. Median parasitaemia was only three parasites per 200 white blood cells (WBC) by routine microscopy compared to 1226 parasites per 200 WBC by expert microscopy. Before RDT implementation, the mean test positivity rates using routine microscopy were 43% in hospitals, 62% in health centres and 58% in dispensaries. After RDT implementation, mean positivity rates using routine RDTs were 6%, 7% and 8%, respectively. The sensitivity and specificity of RDTs using expert microscopy as reference were 97.0% and 96.8%. The positivity rate of routine microscopy remained the same in the three control facilities: 71% before versus 72% after. Two cross-sectional health facility surveys confirmed that the parasite rate in febrile patients was low in Dar es Salaam during both the rainy season (13.6%) and the dry season (3.3%). The quality of routine microscopy was poor in all health facilities, regardless of their level. Over-diagnosis was massive, with many false positive results reported as very low parasitaemia (1 to 5 parasites per 200 WBC). RDTs should replace microscopy as first-line diagnostic tool for malaria in all settings, especially in hospitals where the potential for saving lives is greatest.

114 citations


Journal ArticleDOI
22 Jul 2011-PLOS ONE
TL;DR: These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.
Abstract: BACKGROUND This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children METHODS The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90 RESULTS No serious or severe adverse events (AEs) related to the vaccines were observed The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0014) In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (00035 episodes per day at risk for PEV3B vs 00069 for Inflexal®V; RR = 050 [95%-CI: 029-088], p = 002) CONCLUSION These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines TRIAL REGISTRATION ClinicalTrialsgov NCT00513669

58 citations


Journal ArticleDOI
TL;DR: The quantification obtained by PCR closely correlated with microscopy-based quantification and could be useful for monitoring treatment efficacy, at least in clinical trials.

35 citations


Journal ArticleDOI
TL;DR: This study showed that a motivational brief intervention and/or the provision of free condoms did not modify risky sexual behavior of young travelers, and the rate of inconsistently protected sexual relationships during travel was however lower than expected.
Abstract: Sexually transmitted infections (STIs) are among the frequent risks encountered by travelers. Efficient interventions are needed to improve the understanding of the risks of STIs. We investigated the potential benefits of a motivational brief intervention (BI) and the provision of condoms on the engagement in unprotected casual sex. 3-arm randomized controlled trial performed among single travelers aged 18-44 years visiting a travel clinic in Switzerland. The main outcomes were the prevalence of casual unprotected sexual intercourse and their predictors. 5148 eligible travelers were seen from 2006 to 2008. 1681 agreed to participate and 1115 subjects (66%) completed the study. 184/1115 (17%) had a casual sexual relationship abroad and overall 46/1115 (4.1%) had inconsistently protected sexual relations. Women (adjusted OR 2.7 [95%CI 1.4-5.6]) and travelers with a history of past STI (adjusted OR 2.8 [95%CI 1.1-7.4]) had more frequent casual sexual relationships without consistent protection. Regarding the effect of our intervention, the prevalence of subjects using condoms inconsistently was 28% (95%CI16-40) in the motivational BI group, 24% (95%CI10-37) in the condoms group and 24% (95%CI14-33) in the control group (p = 0.7). This study showed that a motivational brief intervention and/or the provision of free condoms did not modify risky sexual behavior of young travelers. The rate of inconsistently protected sexual relationships during travel was however lower than expected ClinicalTrials.gov: NCT01056536

17 citations


Journal ArticleDOI
12 Jul 2011-Vaccine
TL;DR: The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed, and indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert.

14 citations


Journal Article
TL;DR: A new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999, has been shown to be safe.
Abstract: Many rapid diagnostic tests (RDT) for the diagnosis of infectious diseases have been developed over the last 20 years. These allow (1) administering a treatment immediately in case of a potentially fatal disease, (2) prescribing a specific rather than presumptive treatment, (3) quickly introducing measures aimed at interrupting the transmission of the disease, (4) avoiding useless antibiotic treatments and (5) implementing a sequential diagnostic strategy to avoid extensive investigations. Using the example of malaria, a new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999. This strategy has been shown to be safe. Each TDR has its own characteristics that imperatively need to be known by the practitioner if he/she wants to use it in a rational way

5 citations



Journal Article
TL;DR: A new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999, has been shown to be safe.
Abstract: Many rapid diagnostic tests (RDT) for the diagnosis of infectious diseases have been developed over the last 20 years. These allow (1) administering a treatment immediately in case of a potentially fatal disease, (2) prescribing a specific rather than presumptive treatment, (3) quickly introducing measures aimed at interrupting the transmission of the disease, (4) avoiding useless antibiotic treatments and (5) implementing a sequential diagnostic strategy to avoid extensive investigations. Using the example of malaria, a new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999. This strategy has been shown to be safe. Each TDR has its own characteristics that imperatively need to be known by the practitioner if he/she wants to use it in a rational way.

3 citations


Journal Article
TL;DR: From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot.
Abstract: From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot. ELISA tests are widely used as screening assays since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the different helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient history, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unexplained eosinophilia is present.

2 citations


Journal Article
TL;DR: From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot.
Abstract: From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot. ELISA tests are widely used as screening assays since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the different helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient history, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unexplained eosinophilia is present.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the progress made in terms of diagnostic and traitement of the malaria in the last 10 years and discuss the implications of cette progress on the recommandations de prévention and de traitement for les voyageurs.
Abstract: Si l’on en croit les media, la malaria est le «serial killer number one», les chiffres avancés avoisinant les 500 millions de cas cliniques et le million de décès par année. La situation sur le terrain est bien différente. Des progrès considérables ont en effet été accomplis dans la bataille engagée pour diminuer la malaria. Les avancées principales sont dues au déploiement de stratégies efficaces telles que moustiquaires imprégnées d’insecticide, aspersions intra-domiciliaires et traitements avec des combinaisons à base d’artémisinine. L’utilisation à large échelle des tests de diagnostic rapide et la promesse d’un vaccin disponible dans un proche avenir permettent d’envisager un nouveau paradigme, à savoir l’élimination de la malaria dans plusieurs pays dans les 10 prochaines années. Cet article décrit les données épidémiologiques récentes, ainsi que les innovations en termes de diagnostic et de traitement, sur lesquels se fonde l’espoir d’une éradication éventuelle de la malaria. Les implications de cette évolution sur les recommandations de prévention et de traitement pour les voyageurs sont abordées dans cet article.

01 Jan 2011
TL;DR: Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period and when an unex-plained eosinophilia is present.
Abstract: , and the immunoblot. ELISA tests are widely used as screening as-says since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the diffe-rent helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient his-tory, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unex-plained eosinophilia is present.

Journal ArticleDOI
02 Nov 2011
TL;DR: Seine Rolle bei der Behandlung schwerer Malariafalle bei Reisenden muss allerdings angesichts des in einer neuen europaischen Studie gefundenen Hamolyserisikos noch genauer abgeklart werden.
Abstract: Quintessenz: Malaria ist wahrend der letzten zehn Jahre dank breiter Anwendung von Praventionsmassnahmen (mit Insektiziden impragnierte Moskitonetze, Sprays in Wohnungen) und wirksamer Behandlung in uber 50 Landern um fast die Halfte zuruckgegangen. Wie Plasmodium falciparum kann auch Plasmodium vivax eine Malariaerkrankung mit schweren Symptomen hervorrufen und in Endemiegebieten zu erheblicher Mortalitat fuhren. Diagnostische Schnelltests haben die Behandlung fieberhafter Erkrankungen in Endemiegebieten massiv verbessert, und bei Reisenden kann mit der Behandlung sofort begonnen werden. Kombinationen auf der Basis von Artemisinin sind sehr wirksam zur Behandlung von Malariaattacken, sowohl durch Plasmodium falciparum wie vivax, bei letzterem in Kombination mit Primaquin. I.v.-Artesunat ist dem Chinin zur Behandlung von schwerer Malaria bezuglich Mortalitat deutlich uberlegen. Seine Rolle bei der Behandlung schwerer Malariafalle bei Reisenden muss allerdings angesichts des in einer neuen europaischen Studie gefundenen Hamolyserisikos noch genauer abgeklart werden.